Pursuing a precision medicine approach to discover disease-modifying treatments for neurodegeneration caused by protein misfolding.

Our approach: “Fixing broken proteins”

Origami’s approach is to (1) focus on genetic diseases, (2) use small molecule therapeutics directed at the mutated disease-causing protein, (3) leverage the natural history of the disease to select which patients to treat, when to intervene and what clinical outcomes to measure and (4) demonstrate therapeutic benefit via streamlined clinical trials.

Our Technology

Proteins arising from genes with mutations may have an altered shape (also called conformation), resulting in defective protein processing and a subsequent cascade of deleterious consequences. Our technology platform integrates recent advances in disease biology, cell biology and biophysics, using patient-derived disease models and machine learning to optimize small molecule drugs. Our platform enables discovery of both protein degraders and conformation correctors. This allows us to match the best drug mechanism to each disease in order to achieve the best patient outcome.

Protein misfolding

Disease Areas

Origami’s core technology is capable of addressing a variety of diseases. Our initial indication is Huntington’s disease.

Huntington’s Disease (HD)

HD is caused by a trinucleotide repeat expansion in the Huntingtin gene (HTT) that causes an expanded stretch of a single amino acid, glutamine, in the Huntingtin protein (HTT). A causal link exists between this known mutation and the clinical manifestations.

HD is our first disease target because it aligns with our strategy to focus on genetic diseases and use small molecule therapeutics directed at the mutated disease-causing protein.

brainHuntington’s disease (HD) is a fatal hereditary neurodegenerative disorder that results in a loss of cognitive, behavioral and physical control.

compassionHD slowly diminishes the affected individual’s ability to walk, think, talk and reason. Symptoms usually appear in an individual between 30 and 50 years of age and progresses over a 10 to 25 year period. Eventually, a person with HD becomes totally dependent upon others for his or her care.

chartMore than 70,000 people in the United States and Europe are currently symptomatic with HD and another ~250,000 at risk for HD. Each child of a person with HD has a 50% chance of inheriting the disease.

pillsAlthough medications can partially relieve some symptoms in certain individuals, no treatment is available to conquer or even slow the deadly progression of HD.




Our Company

Founded in 2015, Origami Therapeutics Inc. is a discovery stage company pursuing a precision medicine approach to treat neurological diseases. We are using cutting edge advances in cellular, structural and translational biology to develop protein degraders that prevent HD pathology and reduce mutated protein We have also identified potential conformation correctors that restore normal function. Origami plans to generate a pipeline of small molecule therapeutics for different neurological diseases that prevent or delay the onset and the progression of neurodegenerative diseases to improve the quality of patients’ lives.


Beth J. Hoffman, Ph.D. is Founder, President and CEO
Beth J. Hoffman, Ph.D. is Founder, President and CEO of Origami Therapeutics, Inc. Prior to Origami, she was the Vice President, Discovery Biology for Vertex Pharmaceuticals, Inc. with responsibility for driving strategic planning and execution to generate clinical candidates for respiratory and neurological diseases. Her most significant contributions included the launch of four first-in-class drugs for Cystic Fibrosis (Kalydeco, Orkambi, Symdeko, Trikafta) with a current market of >$4.5B. These therapeutics created a paradigm shift in the Cystic Fibrosis (CF) field by focusing on the underlying cause of the disease using small molecules to modulate protein folding and protein conformation. During her tenure she directly contributed to the first FDA-approved label expansions using preclinical data, enlarging the market for Orkambi and increasing sales to over $1 billion. In addition, she led the research generating a novel non-opioid pain therapeutic, with 3 positive Phase II trials, now entering Phase 3 development, and 2 other protein folding programs to preclinical in vivo proof of concept. At Origami, Dr. Hoffman is leveraging lessons learned from her efforts at Vertex San Diego and 25 years of CNS drug discovery to pursue a new approach to drug discovery for neurodegenerative diseases by modulating folding of disease-causing proteins. Prior to Vertex, she was a Research & Development executive at Amgen and Eli Lilly & Co. She has led and overseen programs from target identification to Phase II proof-of-concept and has managed numerous collaborations with biotech and academic institutions. She has made major contributions to 30 assets that have advanced to the clinic in CF, metabolism, neurology, pain and psychiatry. Dr. Hoffman received an A.B. in Molecular Biology from Wellesley College and a Ph.D. in Cell Biology from Johns Hopkins University.

In the non-profit sector, Dr. Hoffman serves on the Board of Directors for the San Diego Chapter of the Huntington’s Disease Society of America (HDSA).

Leslie J. Schulze, CPA, CGMA is Co-Founder and CFO
Leslie J.  Schulze, CPA, CGMA is Co-founder and CFO of Origami. She has over 20 years of accounting and finance experience, primarily as a senior biotech executive in start-up pharmaceutical R&D companies. Ms. Schulze has played a key role in numerous venture capital (VC) financings (>$140M), non-dilutive fundings (including a government contract for up to $90M and multiple grants), corporate collaborations (up to $1.2B in milestones and royalties), mergers and acquisitions (>$700M, including managing $56M development budget post-acquisition for buyer), asset acquisitions/sales (>$750M), and the development of corporate infrastructure. Ms. Schulze formed Cornerstone Business Solutions, Inc. in 2014 to provide CFO-level finance, accounting, and operations consulting services to start-up biotech companies. During this period, highlights of Ms. Schulze’s activities include: (1) setup new biotech entity, Tripex Pharma LLC, to re-acquire a drug (Quinsair) from Allergan that was then sold to Raptor Pharmaceuticals (now Horizon Pharma) in 2015 for up to $418M plus royalties (Quinsair is approved in CA & EMA), (2) sale of Patara Pharma’s assets to Respivant Sciences, a subsidiary of Roivant Sciences in 2018 for up to $342M plus royalties with subsequent role as interim CFO for Respivant Sciences, including establishment of company accounting policies and reporting and recruitment of permanent finance and accounting teams, and (3) establishment of accounting and reporting policies, recruitment of G&A and research employees, budgeting and managing existing Seed funding and anticipated Series A financing at Therini Bio (formerly MedaRed). Prior to Cornerstone, Ms. Schulze was Co-founder and Vice President Finance and Administration at Rempex Pharmaceuticals, Inc., which was acquired by The Medicines Company in 2013 for up to $474M (Vabomere approved is approved in US, EMA & other countries). Prior to Rempex in 2011, Ms. Schulze served as Controller and Director of Finance at Mpex Pharmaceuticals, Inc., which was acquired by Axcan Holdings, Inc. (now Allergan) in 2011 for up to $230M plus royalties. Prior to Mpex, Ms. Schulze was an Audit Manager at CBIZ Mayer Hoffman McCann, where she specialized in auditing small to mid-sized companies. Ms. Schulze received her bachelor’s degree in Accountancy from the University of San Diego and is a Certified Public Accountant and Chartered Global Management Accountant.
Lucia Mokres, DVM
Lucia Mokres, DVM is Vice President, Regulatory, Clinical and Medical Affairs. She is a Biotechnology Entrepreneurial Consultant based in the Bay Area, specializing in helping early stage companies with novel technology gain traction and develop an investable technology and business model. Prior to establishing her consultancy, she was the Chief Medical Officer of EpiBiome, Inc., a precision microbiome engineering company that employs a genomics approach to profiling complex microbial communities, and deploys bacterial viruses to selectively eliminate problematic bacteria without the use of small-molecule antibiotics in humans, animals, and plants. In this role she leveraged her clinical, research, and industry background to provide medical oversight and strategic direction for all clinical development activities, defined regulatory strategy, supported marketing and business development activities, and served as the medical point of contact for external stakeholders. She led EpiBiome through the iCorps program (UCSF), the Springboard Accelerator program, and supported the team through Johnson and Johnson Innovations JLABS, Illumina Accelerator, and the California Life Sciences Institute FAST Advisory Program.

Prior to joining EpiBiome, she served as a Principal Clinical Scientist and medical advisor at Evalve (acquired in 2010 by Abbott Vascular), supporting medical safety and development of the MitraClip, a minimally invasive device used to reduce mitral regurgitation without the need for open heart surgery. Prior to joining Evalve, she served as a Program Specialist at Hantel Technologies, a contract medical device engineering and manufacturing firm, serving as a liaison between clients and internal departments, and managing timelines and budgets for projects ranging from single person startups to Fortune 500 companies. She completed her postdoctoral fellowship at Stanford University School of Medicine in the Department of Pediatrics.


 David H. Crean
David H. Crean, Ph.D., MBA
David H. Crean, Ph.D., MBA is a Managing Director & Partner at Objective Capital Partners where he leads the firm’s investment banking transactions with life science and healthcare clients. Dr. Crean has in excess of 25 years of life sciences R&D and corporate development transactional experience in the pharmaceutical industry responsible for leading mergers, acquisitions, licensing and collaborations, and establishing corporate strategy.

Dr. Crean also serves as a business advisor for several early stage life science companies, is a limited partner with Mesa Verde Venture Partners Fund, on the Board of Directors for the Association for Corporate Growth (ACG) in San Diego, Capital Development Committee for BIOCOM, and a member of San Diego Venture Group (SDVG) and Corporate Directors Forum. Recently, he was recognized and awarded Thought Leader of the Year and Advisor of the Year in 2017 for his advisory guidance to executives in life sciences deals. Dr. Crean is also active in the non-profit sector where he serves in leading Board roles for Solutions for Change, Alzheimer’s Association and Altus Charter Schools of San Diego.

Dr. Crean holds a Masters of Business Administration (MBA) Degree with a finance concentration from Pepperdine University Graziadio School of Management. Additionally, he holds a Doctorate of Philosophy (Ph.D.) Degree in Biophysics and a Masters of Science (MS) Degree in Oncology from the State University of New York at Buffalo. Dr. Crean also earned a Bachelor of Science (BS) Degree in Biology/ Pre-Med from Canisius College.

Steven Finkbeiner, M.D., Ph.D.
Steven Finkbeiner, M.D., Ph.D., is Director, Taube/Koret Center for Neurodegenerative Disease Research and the Center for Systems and Therapeutics at the Gladstone Institutes, Investigator, Roddenberry Stem Cell Center and Professor, Neurology and Physiology, University of California, San Francisco. He is best known for his pioneering work on neurodegenerative diseases. Dr. Finkbeiner invented robotic microscopy, a new form of imaging that has helped unravel cause-and-effect relationships in amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease), Huntington’s, Parkinson’s, Alzheimer’s and other neurodegenerative diseases. He has used his robotic microscope to resolve the long-standing puzzle in Huntington’s disease. Dr. Finkbeiner studies the molecular mechanisms that are responsible for learning, memory, and neurodegeneration.

In conjunction with Bay Area philanthropists, Dr. Finkbeiner established the Taube/Koret Center in 2009 to accelerate development of drug therapies for patients suffering from conditions such as Huntington’s disease. At Gladstone, he also directs the Hellman Family Foundation for Alzheimer’s Disease Research Program. Dr. Finkbeiner has received numerous awards including the Lieberman Award, the Taube/Koret Prize and the Award for Outstanding Research Achievement from Nature Biotechnology. He is a member of the American Neurological Association, the Society for Neuroscience, the Society for Cell Biology and the Biophysical Society.

Dr. Finkbeiner is Associate Editor of Autophagy and serves on the editorial board of the Journal of Huntington’s Disease. He earned a bachelor’s degree from Wheaton College and both an MD and a PhD in neuroscience from Yale University.

Kalpana Merchant, Ph.D.

Kalpana Merchant, Ph.D. is President and CSO, TransThera Consulting Co, Adjunct Professor, Dept of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA, Adjunct Professor, Dept of Biology, Purdue University School of Science, Indiana University-Purdue University, Indianapolis, IN, USA.

Dr. Merchant has deep expertise in the neurobiology of chronic neurodegenerative and psychiatric disorders. She has nearly 25 years of experience in drug discovery and development with a special emphasis on translational strategies. She retired in March 2014 from Eli Lilly where she was the Chief Scientific Officer for Tailored Therapeutics-Neuroscience, accountable for strategies to deliver personalized therapies and associated biomarkers for the neuroscience portfolio.

Since 2014 Kalpana has engaged with non-profit foundations and start-up pharmaceutical companies as an advisor. In 2018, she joined Vincere Biosciences, as the Chief Scientific Officer to help develop small molecules to slow the progression of Parkinson’s disease.
Kalpana received her PhD in neuropharmacology from the University of Utah in 1989. Following a postdoctoral fellowship at University of Washington, she remained at the Institute as Assistant Professor of Psychiatry. She joined Eli Lilly in 2003 after contributing to neuroscience drug discovery research at Pharmacia Corp. for ~10 years.

Origami Therapeutics, Inc.

A resident company of JLABS @ San Diego

Lab Address:
3210 Merryfield Row
San Diego, CA 92121

Mailing Address:
3525 Del Mar Heights Road, Suite 938
San Diego, CA 92130

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